This proposal outlines a Multi-Institutional Collaborative Research (R-10) Project in which we will evaluate the risk of relapse in pregnancy among women with a history of major depression who either maintain or discontinue antidepressant treatment around the time of conception. The primary aims of this investigation are (1) to establish whether relapse/recurrence rates are lower in women who maintain versus discontinue antidepressant treatment during pregnancy; (2) to identify clinical and psychosocial predictors of relapse during pregnancy in those who maintain or discontinue antidepressants; and (3) to assess perinatal outcome and its relationship to depressive symptomatology in pregnancy. The three participating sites for this investigation include the Perinatal and Reproductive Psychiatry, Clinical Research Program, Massachusetts General Hospital, Harvard Medical School (Dr. Cohen), Women's Life Center and Mood Disorders Research, UCLA (Dr. Altshuler), Emory University School of Medicine (Dr. Stowe). Subjects who have euthymic for at least three months and who have not discontinued antidepressant more than six weeks prior to conception will be accessioned early in their pregnancy and will be followed longitudinally from the first trimester of pregnancy through delivery. Given the prevalence of major depression during the childbearing years and the growing numbers of women who receive treatment with antidepressants, it is crucial to identify those women who may be able to safely discontinue antidepressant treatment during pregnancy as well as those who are particularly vulnerable to relapse. Delineating of these subgroups provides an opportunity to screen for women "at risk" for relapse and allows for thoughtful treatment plan.